Microfluidic chip with coating to reduce fluid diffusion and method of manufacturing same

ABSTRACT

A microfluidic chip is disclosed herein. In an embodiment, the microfluidic chip includes a body including at least one microfluidic pathway configured to receive a fluid sample, the at least one microfluidic pathway including a coating configured to reduce fluid diffusion and seal a surface of the at least one microfluidic pathway, and a heating device located on the body and forming a heating zone within a portion of the at least one microfluidic pathway.

CROSS REFERENCE TO RELATED APPLICATION

The present application is a continuation of U.S. patent applicationSer. No. 14/934,794, entitled “Microfluidic Chips with OpticallyTransparent Glue Coating and a Method of Manufacturing MicrofluidicChips with Optically Transparent Glue Coating for a MicrofluidicDevice,” filed Nov. 6, 2015, which is a continuation of U.S. patentapplication Ser. No. 14/028,320, entitled “Microfluidic Chips withOptically Transparent Glue Coating and a Method of ManufacturingMicrofluidic Chips with Optically Transparent Glue Coating for aMicrofluidic Device,” filed Sep. 16, 2013, now U.S. Pat. No. 9,180,652,the entire contents of each of which is hereby incorporated by referenceherein.

BACKGROUND OF THE DISCLOSURE

Field of Disclosure

The present disclosure relates generally to a method of manufacturingmicrofluidic chips for handling fluid samples on a microfluidic level,and, more specifically, to a method of manufacturing microfluidic chipswith coating to reduce fluid diffusion and microfluidic chips with acoating to reduce fluid diffusion. The manufactured microfluidic chipscan be used to perform real-time analysis, for example, polymerase chainreaction (PCR) analysis.

Discussion of the Related Art

Microfluidics can be used in medicine or cell biology researches andrefers to the technology that relates to the flow of liquid in channelsof micrometer size. At least one dimension of the channel is of theorder of a micrometer or tens of micrometers to be considered asmicrofluidics. In particular, microfluidic devices are useful formanipulating or analyzing micro-sized fluid samples on microfluidicchips, with the fluid samples typically in extremely small volumes downto less than picoliters.

When manipulating or analyzing fluid samples, fluids are pumped onto themicro-channel of microfluidic chips in doses or are continuously flowedonto the micro-channel of microfluidic chips. If the fluid sample ispumped in doses, the fluid sample stays in the micro-channel of themicrofluidic chip until the fluid sample is suctioned out from themicro-channel. The fluid sample can be manipulated or analyzed whilebeing held in the micro-channel.

Alternatively, for continuous flow analysis, the fluid is pumpedcontinuously into the micro-channel. Due to the continuous fluidpumping, the fluid sample instead flows and travels through themicro-channel and exits the micro-channel when reaches the outlet of themicro-channel. The fluid sample can be manipulated or analyzed whileflowing through the micro-channel, and one can perform a biochemicalreaction examination on the continuously flowing fluid sample, includingtreating and manipulating processes of the fluid.

Presently, microfluidic chips have micro-channels molded inPolyDiMethyiSiloxane (“PDMS”). The micro-channels then are sealed whenthe PDMS block is bonded to a glass slide.

FIGS. 1A-1D are perspective views of manufacturing a microfluidic chipmold according to the related art. The manufacturing of a microfluidicchip according to the related art takes a channel design and duplicatesthe channel design onto a photomask 10. As shown in Figure IA, aphotoresist 22 is deposited onto a semiconductor wafer 20. As shown inFIG. 1B, the photomask 10 that reflects the channel design 12 is placedover the wafer 20, and the wafer 20 with the mask 10 undergoes UVexposition to cure the photoresist 22. Then, as shown in FIG. 10, thewafer 20 with the cured photoresist 22′ is developed. The ‘negative’image of a channel according to the channel design is etched away fromthe semiconductor wafer 20. As shown in FIG. 1D, after all residualphotoresist are removed, the resulting wafer becomes a mold 20′ thatprovides the channel according to the channel design 12′.

FIG. 2 are perspective views of the steps of manufacturing amicrofluidic chip according to the related art. As shown in FIG. 2, PDMSin liquid form 30 is poured onto the mold 20′. Liquid PDMS 30 may bemixed with crosslinking agent. The mold 20′ with liquid PDMS 30 is thenplaced into a furnace to harden PDMS 30. As PDMS is hardened, thehardened PDMS block 30′ duplicates the micro-channel 12″ according tothe channel design. The PDMS block 30′ then may be separated from themold 20′. To allow injection of fluid into the micro-channel 12″ (whichwill subsequently be sealed), inlet or outlet is then made in the PDMSblock 30′ by drilling into the PDMS block 30′ using a needle. Then, theface of the PDMS block 30′ with micro-channels and a glass slide 32 aretreated with plasma. Due to the plasma treatment, the PDMS block 30′ andthe glass slide 32 can bond with one another and close the chip.

The microfluidic chip according to the related all has a micro-channelin the PDMS block. PDMS belongs to a group of polymeric organosiliconcompounds that are commonly referred to as silicone, and can bedeposited onto the master mold in liquid form and subsequently hardened.

However, PDMS is inherently porous and due to its polymer structure,PDMS is highly permeable. Thus, diffusion of fluid sample through PDMShas been observed. Such diffusion of fluid sample does not impact amicrofluidic system that pumps fluid samples in doses as significantlyas a continuous flow microfluidic system. In particular, when acontinuous flow microfluidic system monitors treating and manipulatingof the flowing fluid in real-time analysis applications, diffusion orunaccounted loss of fluid sample can significantly impact the real-timeanalysis. Thus, there exists a need for reducing diffusion or loss offluid sample in micro-channel of a microfluidic chip.

SUMMARY OF THE DISCLOSURE

Accordingly, embodiments of the present disclosure are directed to amethod of manufacturing microfluidic chips for handling fluid samples ona microfluidic level and microfluidic chips that can substantiallyobviate one or more of the problems due to limitations and disadvantagesof the related art.

An object of embodiments of the present disclosure is to provide amethod of manufacturing microfluidic chips to reduce fluid diffusion inmicro-channel, and microfluidic chips manufactured using the same.

An object of embodiments of the present disclosure is to provide amethod, of manufacturing microfluidic chips with micro-channel coating,and microfluidic chips manufactured using the same.

Additional features and advantages of embodiments of the presentdisclosure will be set forth in the description which follows, and inpart will be apparent from the description, or may be learned bypractice of embodiments of the present disclosure. The objectives andother advantages of the embodiments of the present disclosure will berealized and attained by the structure particularly pointed out in thewritten description and claims hereof as well as the appended drawings.

To achieve these and other advantages and in accordance with the purposeof embodiments of the present disclosure, as embodied and broadlydescribed, a microfluidic chip device according to an embodiment of thepresent disclosure includes a substrate having a first thickness, atleast one microfluidic pathway in the substrate, a coating along themicrofluidic pathway, and a glass layer having a second thickness on thesubstrate and above the microfluidic pathway, wherein the coatingcontains cyanoacrylates, and the first thickness is greater than thesecond thickness.

In accordance with another embodiment of the present disclosure, asembodied and broadly described, a microfluidic chip device includes asubstrate having a first thickness, at least one microfluidic pathway inthe substrate, a coating along the microfluidic pathway, and a glasslayer having a second thickness on the substrate and above themicrofluidic pathway, wherein the coating contains an opticallytransparent material, and the first thickness is greater than the secondthickness.

In accordance with another embodiment of the present disclosure, asembodied and broadly described, a method for manufacturing amicrofluidic chip device includes etching a substrate having a firstthickness for forming at least one microfluidic pathway in thesubstrate, coating the substrate, and bonding a glass layer having asecond thickness on the substrate and above the microfluidic pathway,wherein the step of coating includes coating an optically transparentmaterial, and the first thickness is greater than the second thickness.

In accordance with another embodiment of the present disclosure, asembodied and broadly described, a microfluidic chip device includes acoating along the microfluidic pathway, wherein the coating includescyanoacrylates, an UV curable epoxy adhesive, a gel epoxy or epoxy undertrade name of EPO-TEK OG175, MasterBond EP30LV-1 or Locite 0151.

In accordance with another embodiment of the present disclosure, asembodied and broadly described, a method for manufacturing amicrofluidic chip device includes etching a substrate having a firstthickness for forming at least one microfluidic pathway in the substrateand coating along the microfluidic pathway, wherein the coating includescoating with cyanoacrylates, an UV curable epoxy adhesive, a gel epoxyor epoxy under trade name of EPO-TEK OG1.75, MasterBond EP30LV-1 orLocite 0151.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory and areintended to provide further explanation of embodiments of the presentdisclosure as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a furtherunderstanding of embodiments of the present disclosure and areincorporated in and constitute a part of this specification, illustrateembodiments of the present disclosure and together with the descriptionserve to explain the principles of embodiments of the presentdisclosure.

FIGS. 1A-1D are perspective views of manufacturing a microfluidic chipmold according to the related art.

FIG. 2 illustrates the steps of manufacturing a microfluidic chipaccording to the related art.

FIG. 3 is a perspective view of a microfluidic chip for a microfluidicsystem according to an embodiment of the present disclosure.

FIG. 4 is a side view of the microfluidic chip shown in FIG. 3.

FIG. 5 is a side view of the microfluidic chip according to anotherembodiment of the present disclosure.

FIG. 6 is a top view of a heater for a microfluidic chip of amicrofluidic system according to an embodiment of the presentdisclosure.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Reference will now be made in detail to the preferred embodiments of thepresent disclosure, examples of which are illustrated in theaccompanying drawings.

FIG. 3 is a perspective view of a microfluidic chip for a microfluidicsystem according to an embodiment of the present disclosure, and FIG. 4is a side view of the microfluidic chip shown in FIG. 3. As shown inFIGS. 3 and 4, a microfluidic chip 100 includes a PDMS substrate 110 anda glass layer 120 on the substrate 110. The glass layer 120 may beformed of borosilicate. As shown in the substrate 110. For instance, theglass layer 120 may have a thickness of about 0.01 inch or less.

The substrate 110 includes micro-channels 130. The micro-channels 130form a microfluidic pathway, and the channels allow fluid samples to beflowed through therein. The micro-channels 130 may be formed by etchingthe substrate 110.

After the micro-channels 130 are formed in the substrate 110 but priorto sealing micro-channels 130 with the glass layer 120, the substrate110 is coated with cyanoacrylates 112 to seal the surface pores of thesubstrate 110. Cyanoacrylates are acylic resin and are mainly used asadhesives. However, cyanoacrylates are not used as adhesives in themicro-channels of the substrate 110. Instead, cyanoacrylates are allowedto set to form a coating along the micro-channels 130.

When coating the substrate 110, the amount of cyanoacrylates depositedis controlled so as not to fill the micro-channels 130 of the substrate110. In addition or alternatively, the micro-channels 130 are formedwider and/or deeper in the substrate 110 to account for the subsequentcoating thickness of cyanoacrylates 112.

The microfluidic chip 100 further includes heaters 140 a, 140 b and 140c. For example, the heaters 140 a, 140 b and 140 c may be resistiveheating devices, such as thin-film heaters. The heaters 140 a, 140 b and140 c may be formed by applying a thin film of conductive materialdirectly on the glass layer 120. For example, the heaters 140 a, 140 band 140 c may include aluminum. More specifically, the heaters 140 a,140 b and 140 c may have a thickness of about 0.001 inch or less.

The microfluidic chip 100 further includes temperature sensors 150 a,150 b and 150 c. For example, the temperature sensors 150 a, 150 b and150 c may be resistance temperature detectors. The temperature sensors150 a, 150 b and 150 c provide real-time temperature detection to morethan one zones or portions of the microfluidic chip 100. The real-timetemperature detection is then used to control heaters 140 a, 140 b and140 c, respectively. As such, the microfluidic chip 100 may haveindependently-temperature-controlled zones.

A microprocessor (not shown) may be connected to the temperature sensors150 a, 150 b and 150 c and the heaters 140 a, 140 b and 140 c to provideindependently-temperature-controlled zones for the microfluidic chip100. For example, the microprocessor may implement a control algorithm,such as PID control to receive temperature inputs from the temperaturesensors 150 a, 150 b and 150 c and dynamically controls the output ofthe heaters 140 a, 140 b and 140 c.

For real-time analysis, an optical sensor 160 is further included andcan be placed above or below the microfluidic chip 100. The opticalsensor 160 provides real-time monitoring of the manipulation of thefluid sample in the micro-channel 130 of the microfluidic chip 100. Thesame microprocessor (not shown) can also receive and control the opticalsensor 160.

FIG. 5 is a side view of the microfluidic chip according to anotherembodiment of the present disclosure. In FIG. 5, a microfluidic chip100′ includes a layer of cured optically transparent material 112′between a substrate 110′ and a seal layer 120′. As shown in FIG. 3, thethickness of the seal layer 120′ is much smaller than the thickness ofthe substrate 110′. For instance, the seal layer 120′ may have athickness of about 0.01 inch or, less.

The substrate 110′ includes micro-channels 130′. The micro-channels 130′form a microfluidic pathway, and the channels allow fluid samples to beflowed through therein. The micro-channels 130′ may be formed by etchingthe substrate 110′.

After the micro-channels 130′ are formed in the substrate 110′ but priorto sealing micro-channels 130′ with the seal layer 120′, the substrate110′ is coated with an optically transparent material to seal thesurface of the substrate 110′. The optically transparent material isallowed to set or hardened to form the layer of cured opticallytransparent material 112′. An UV curable epoxy adhesive, a gel epoxy orepoxy under trade name of EPO-TEK OG175, MasterBond EP30LV-1 or Locite0151 may be used to coat the surface of the substrate 110′.

When coating the substrate 110′, the amount of the optically transparentmaterial deposited are controlled so as not to fill the micro-channels130′ of the substrate 110′. In addition or alternatively, themicro-channels 130′ are formed wider and/or deeper in the substrate 110′to account for the subsequent layer of cured optically transparentmaterial 112′.

The microfluidic chip 100′ further includes heaters 140 a′, 140 b′ and140 c′. For example, the heaters 140 a′, 140 b′ and 140 c′ may beresistive heating devices, such as thin-film heaters. The heaters 140a′, 140 b′ and 140 c′ may be formed by applying a thin film ofconductive material directly on the seal layer 120′. For example, theheaters 140 a′, 140 b′ and 140 c′ may include aluminum. Morespecifically, the heaters 140 a′, 140 b′ and 140 c′ may have a thicknessof about 0.001 inch or less.

The microfluidic chip 100′ further includes temperature sensors 150 a′,and 150 c′. For example, the temperature sensors 150 a′, 150 b′ and 150c′ may be resistance temperature detectors. The temperature sensors 150a′, 150 b′ and provide real-time temperature detection to more than onezones or portions of the microfluidic chip 100′. The real-timetemperature detection is then used to control heaters 140 a′, 140 b′ and140 c′, respectively. As such, the microfluidic chip 100 may haveindependently-temperature-controlled zones.

A microprocessor (not shown) may be connected to the temperature sensors150 a′, 150 b′ and 150 c′ and the heaters 140 a′, 140 b′ and 140 c′ toprovide independently-temperature-controlled zones for the microfluidicchip 100′. For example, the microprocessor may implement a controlalgorithm, such as PID control to receive temperature inputs from thetemperature sensors 150 a′, 150 b′ and 150 c′ and dynamically controlsthe output of the heaters 140 a′, 140 b′ and 140 c′.

Although not shown, for real-time analysis, an optical sensor is furtherincluded and can be placed above or below the microfluidic chip 100′.The optical sensor provides real-time monitoring of the manipulation ofthe fluid sample in the micro-channel 130′ of the microfluidic chip100′. The optical sensor may be controlled by a microprocessor.

FIG. 6 is a top view of a heater for a microfluidic chip of acontinuous-flow microfluidic system according to an embodiment of thepresent disclosure. As shown in FIG. 6, a thin-film heater 140 for amicrofluidic chip of a microfluidic system preferably may include twoelectrical interface pads 142 a and 142 b. The two electrical interfacepads 142 a and 142 b may receive voltage and/or current. Morespecifically, electrical resistance or heat may be generated by thethin-film heater 140 based on V²/R or I²×R. Such heat may providetemperature to the channels 130 or 130′ shown in FIG. 4 or 5.

Preferably, the thin-film heater 140 is spread above the channels 130 or130′ evenly to provide consistent heating of the channel below. Thethin-film heater 140 may have a line-like shape between the twoelectrical interface pads 142 a and 142 b. For example, the thin-filmheater 140 may have elongated strips that are substantially parallelwith one another.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the microfluidic chip ofembodiments of the present disclosure without departing from the spiritor scope of the present disclosure. Thus, it is intended thatembodiments of the present disclosure cover the modifications andvariations of this disclosure provided they come within the scope of theappended claims and their equivalents.

What is claimed: 1: A microfluidic chip comprising: a body including atleast one microfluidic pathway configured to receive a fluid sample, theat least one microfluidic pathway including a coating configured toreduce fluid diffusion and seal a surface of the at least onemicrofluidic pathway; and a heating device located on the body andforming a heating zone within a portion of the at least one microfluidicpathway. 2: The microfluidic chip of claim 1, wherein the body includesat least two layers, the at least one microfluidic pathway formedbetween the at least two layers. 3: The microfluidic chip of claim 1,wherein the body is formed of multiple layers, the at least onemicrofluidic pathway formed on a first side of a first layer of themultiple layers, the heating device located on an opposite second sideof the first layer. 4: The microfluidic chip of claim 3, wherein theheating device includes a layer of conductive material applied to thesecond side of the first layer. 5: The microfluidic chip of claim 3,wherein at least a portion of the at least one microchannel is etchedinto a second layer attached to the first side of the first layer. 6:The microfluidic chip of claim 1, wherein the heating device includes aresistive heating device. 7: The microfluidic chip of claim 1, whereinthe heating device includes a layer of conductive material applied to anouter surface of the body. 8: The microfluidic chip of claim 1, whichincludes a plurality of heating devices forming a plurality ofindependent heating zones within separate portions of the at least onemicrochannel. 9: The microfluidic chip of claim 1, wherein the heatingdevice is configured to be connected to a microprocessor to enable themicroprocessor to control the temperature of the fluid sample within theat least one microfluidic pathway by controlling the heating device. 10:The microfluidic chip of claim 9, wherein the microprocessor furthercontrols an optical device to perform an optical analysis of the fluidsample. 11: A microfluidic system comprising: a microfluidic chipincluding a first side and a second side, the microfluidic chipincluding at least one microfluidic pathway for a fluid sample to flowthrough, the at least one microfluidic pathway including a coatingconfigured to reduce fluid diffusion and seal a surface of the at leastone microfluidic pathway; and a microprocessor configured to cause (i)the fluid sample within the at least one microfluidic pathway to beheated from the first side of the microfluidic chip, and (ii) the fluidsample within the at least one microfluidic pathway to be opticallyanalyzed from the second side of the microfluidic chip. 12: Themicrofluidic system of claim 11, which includes a heating device on thefirst side of the microfluidic chip, the heating device configured to beconnected to the microprocessor. 13: The microfluidic system of claim12, wherein the heating device is part of the microfluidic chip. 14: Themicrofluidic system of claim 13, wherein the heating device includes alayer of conductive material applied to the first side of themicrofluidic chip. 15: The microfluidic system of claim 11, wherein thefirst and second sides of the microfluidic chip are opposite sides ofthe microfluidic chip. 16: A microfluidic chip comprising: a body formedof at least a first layer having a first thickness and a second layerhaving a second thickness, the first thickness greater than the secondthickness; at least one microfluidic pathway etched into the body andconfigured to receive a fluid sample; and a coating configured to reducefluid diffusion and seal a surface of the at least one microfluidicpathway, the coating exposed along the at least one microfluidic pathwayto reduce fluid diffusion as the fluid sample flows through the at leastone microfluidic pathway. 17: The microfluidic chip of claim 16, whereinthe first layer is a same length and width as the second layer. 18: Themicrofluidic chip of claim 16, wherein the at least one microfluidicpathway is located on a first side of the second layer, and whichincludes a heating device located on an opposite second side of thesecond layer. 19: The microfluidic chip of claim 18, wherein the heatingdevice includes a layer of conductive material applied to the secondside of the second layer. 20: The microfluidic chip of claim 16, whereinat least the first layer is optically transparent to enable an opticalanalysis of the fluid sample.